1 HEMOPHORE HASA Nadia Izadi-Pruneyre, Nicolas Wolff, Muriel Delepierre and Anne Lecroisey Unité de Résonance Magnétique Nucléaire des Biomolécules, CNRS URA 2185, Institut Pasteur, Paris, France Keywords: heme binding; hemophore; bacterial iron uptake; TonB dependent transporter; membrane transport; protein-protein interaction Abstract: To satisfy their iron needs, several gram-negative bacteria use a heme uptake system that rely on the secretion in the extracellular medium of heme-binding proteins called HasA hemophores. These proteins scavenge heme from the host, either free or hemoprotein-bound, and shuttle it to a specific outer membrane transporter, HasR, whereby it is internalized by a TonB dependent process and then used as iron source. HasA hemophores form a family of highly conserved 19-20 kDa proteins without neither sequential nor structural similarities to other known proteins. The HasA hemophore from Serratia marcescens, the most deeply studied, is described here with a special focus on its heme binding site and its unusual pair of axial ligands, a histidine and a tyrosine. The spectroscopic properties and the structures of the heme loaded and unloaded hemophore, free or complexed to the HasR transporter are presented. The mechanisms of heme capture by the hemophore and heme transfer to HasR are discussed.